Suicidality at Epilepsy Diagnosis Linked to Future Drug Resistance: JAMA

A new study published in the Journal of American Medical Association showed that suicidality at the time of focal epilepsy diagnosis was linked to a greater chance of developing drug-resistant epilepsy in the future and may be a sign of more serious underlying brain illness.

Psychiatric problems are widespread in epilepsy and are related with a higher risk of early death, a worse quality of life, and a poor response to antiseizure drugs (ASMs). Thus, this study assessed the relevance of mental problems at the time of epilepsy diagnosis in predicting the likelihood of future treatment resistance in focal epilepsy.

The Human Epilepsy Project (HEP) had a maximum 6-year follow-up period, where the newly diagnosed focal epilepsy patients (18 to 60 years) registered within 4 months of starting ASM therapy, and had no major additional comorbidities were included. During the open period from 2012 to 2020 the participants were recruited.

The MINI and C-SSRS were completed by 347 (median [IQR] age at seizure start, 33 [23–44] years; 209 female [60.2%]) of the 376 persons who were recruited. Of them, 83 (24%) were TR, 73 (21%) were uncertain, and 191 (55%) were TS. At the time of epilepsy diagnosis, 38% (n = 133) had a mental issue (suicidality, mood/anxiety disease).

75 (22%) had suicidality with or without a mental condition, whereas 57 (16%) had mood/anxiety problem or disorders without suicidality. A higher than two-fold increased chance of developing TR was linked to suicidality at the time of epilepsy diagnosis (relative risk [RR], 2.02; 95% CI, 1.32-3.09; P =.001). Thereby, there were no meaningful correlations found between TR and mood/anxiety problems.

In those without mental disorders, the chance of TR rose from 16.3% (95% CI, 11.3%-21.3%) to 47.1% (RR, 2.89; 95% CI, 1.65-5.05; P <.001) when suicidality was present alone. After adjusting for multiple comparisons, anxiety disorder alone raised the TR likelihood to 32.9% (RR, 2.02; 95% CI, 1.10-3.71; P =.02), although this was not statistically significant.

When mood disorder was present alone, the chance of TR did not significantly alter; however, when mood disorder and suicidality were present, the probability of TR rose to 39.6% (RR, 2.43; 95% CI, 1.26-4.68; P =.008). Overall, the findings of this cohort research show that suicidality at the time of focal epilepsy diagnosis was linked to future medication resistance and may be a predictor of more severe neuropathology. 

Source:

Barnard, S. N., French, J. A., Chen, Z., Holmes, M., Hegde, M., Altalib, H. H., Winawer, M., Sperling, M., Jette, N., Hope, O., Nadkarni, S., O’Brien, T. J., Kuzniecky, R., Lowenstein, D., Kanner, A. M., & Human Epilepsy Project Investigators. (2026). Suicidality at epilepsy diagnosis and future treatment resistance in adults with focal epilepsy. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2026.0204